Exploring uterine involvement in hysterectomy samples following conization for adenocarcinoma in situ of the uterine cervix: Insights from a multicenter study by the FRANCOGYN group.

BACKGROUND: Adenocarcinoma in situ (AIS) of the cervix can progress to invasive adenocarcinoma. While hysterectomy is standard, conservative management may be considered for women desiring future pregnancies. This study aimed to determine the prevalence of residual disease in hysterectomy specimens following excisional therapy with clear margins for AIS. METHODS: A retrospective FRANCOGYN cohort study was conducted on patients who underwent a hysterectomy after conization with clear margins for AIS between 2008 and 2021. The primary goal was to assess the prevalence of residual disease in the hysterectomy specimens. Secondary objectives included identifying preoperative predictors of residual disease and comparing recurrence rates between patients with and without residual disease. RESULTS: Of 53 hysterectomies performed after conization with negative margins for AIS, 20.8% (11/53) showed residual disease in the final histology. None of the patients had invasive cancer. In the residual disease group, 18% (2/11) had persistent CIN 3, and 82% (9/11) had persistent AIS. These patients tended to have higher BMI (27.5 kg/m² vs. 23.6 kg/m², p=0.04) and shorter endocervical margins (2mm vs. 5mm, p=0.01). No recurrences were observed during follow-up. CONCLUSION: Despite clear margins on the initial conization for AIS, 20% of patients had residual disease in their hysterectomy samples, though no invasive cancer was found. A hysterectomy should be considered after completing childbearing, even if initial margins are clear.

Cost-effectiveness of robot-assisted total hysterectomy for benign pathologies compared to laparoscopic surgery: A retrospective study with propensity score.

BACKGROUND: Hysterectomy for benign pathologies is one of the most common gynecological surgeries. In recent years, robotic surgery has become an alternative to traditional surgery, but at a higher cost. OBJECTIVE: Estimate the cost of benign robot-assisted hysterectomy for the purpose of supporting public decision-making, as well as the additional cost per major postoperative complication (ClavienDindo score ≥ 3) avoided one month after surgery robotic versus traditional laparoscopic. METHODS: Single-center retrospective study including patients operated on for benign hysterectomy at La Pitié Salpêtrière hospital between January 2016 and December 2019: 99 by robotic approach, and 86 by laparoscopic approach. Comparison of robotic surgery to laparoscopy. Calculation of a cost-effectiveness ratio (ICER). Use of the propensity score inverse weighting method to ensure comparability of groups. RESULTS: Robotic surgery has a total cost of € 6,615 at 1 month per patient compared to € 3,859 for laparoscopic surgery with an additional cost of € 377,534 per major postoperative complication avoided, longer operating time and an absence of significant difference in terms of complications and length of hospitalization. CONCLUSION: In terms of cost-effectiveness, according to this study, the robot does not appear to be better than laparoscopy. In the years to come, we can expect a development of robotic surgery with rationalization of the practice, with appropriate selection of patients for robotic surgery, development of outpatient surgery and a reduction in the cost of the equipment.

First external validity study of the Fagotti score in ovarian cancer.

Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75-0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.

Brachytherapy and surgery versus surgery alone for IB2 (FIGO 2018) cervical cancers: A FRANCOGYN study.

OBJECTIVE: Evaluation of the management by first brachytherapy followed by radical hysterectomy (Wertheim type) compared to radical hysterectomy alone (Wertheim type) for the treatment of IB2 cervical cancer. METHODS: Data from women with histologically proven FIGO stage IB2 cervical cancer treated between April 1996 and December 2016 were retrospectively abstracted from twelve French institutions with prospectively maintained databases. RESULTS: Of the 211 patients with FIGO stage IB2 cervical cancer without lymph node involvement included, 136 had surgical treatment only and 75 had pelvic lymph node staging and brachytherapy followed by surgery. The surgery-only group had significantly more adjuvant treatment (29 vs. 3; p = 0.0002). A complete response was identified in 61 patients (81%) in the brachytherapy group. Postoperative complications were comparable (63,2% vs. 72%, p = 0,19) and consisted mainly of urinary (36vs. 27) and digestive (31 vs 22) complications and lymphoceles (4 vs. 1). Brachytherapy had no benefit in terms of progression-free survival (p = 0.14) or overall survival (p = 0.59). However, for tumors of between 20 and 30 mm, preoperative brachytherapy improved recurrence-free survival (p = 0.0095) but not overall survival (p = 0.41). This difference was not observed for larger tumors in terms of either recurrence-free survival (p = 0.55) or overall survival (p = 0.95). CONCLUSION: Our study found that preoperative brachytherapy had no benefit for stage IB2 cervical cancers in terms of recurrence-free survival or overall survival. For tumor sizes between 2 and 3 cm, brachytherapy improves progression-free survival mainly by reducing pelvic recurrences without improving overall survival.

Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study.

OBJECTIVES: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival. METHODS: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies. RESULTS: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04). CONCLUSION: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.

Robotic-assisted benign hysterectomy compared with laparoscopic, vaginal, and open surgery: a systematic review and meta-analysis.

The potential benefits and limitations of benign hysterectomy surgical approaches are still debated. We aimed at evaluating any differences with a systematic review and meta-analysis. PubMed, MEDLINE, and EMBASE databases were last searched on 6/2/2021 to identify English randomized controlled trials (RCTs), prospective cohort and retrospective independent database studies published between Jan 1, 2010 and Dec 31, 2020 reporting perioperative outcomes following robotic hysterectomy versus laparoscopic, open, or vaginal approach (PROSPERO #CRD42022352718). Twenty-four articles were included that reported on 110,306 robotic, 262,715 laparoscopic, 189,237 vaginal, and 554,407 open patients. The robotic approach was associated with a shorter hospital stay (p < 0.00001), less blood loss (p = 0.009), and fewer complications (OR: 0.42 [0.27, 0.66], p = 0.0001) when compared to the open approach. The main benefit compared to the laparoscopic and vaginal approaches was a shorter hospital (R/L WMD: - 0.144 [- 0.21, - 0.08], p < 0.0001; R/V WMD: - 0.39 [- 0.70, - 0.08], p = 0.01). Other benefits seen were sensitive to the inclusion of database studies. Study type differences in outcomes, a lack of RCTs for robotic vs. open comparisons, learning curve issues, and limited robotic vs. vaginal publications are limitations. While the robotic approach was mainly comparable to the laparoscopic approach, this meta-analysis confirms the classic benefits of minimally invasive surgery when comparing robotic hysterectomy to open surgery. We also reported the advantages of robotic surgery over vaginal surgery in a patient population with a higher incidence of large uterus and prior surgery.

Value of high-resolution full-field optical coherence tomography and dynamic cell imaging for one-stop rapid diagnosis breast clinic.

BACKGROUND: Full-field optical coherence tomography combined with dynamic cell imaging (D-FFOCT) is a new, simple-to-use, nondestructive, quick technique that can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. METHODS: Dynamic full-field optical coherence tomography was applied to fresh, untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon, and pathologist) analyzed the samples without knowing final histological diagnosis or American College of Radiology classification. The results were compared to conventional processing and staining (hematoxylin-eosin). RESULTS: A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49.27%), 99 benign lesions (48.29%), 3 ductal in situ carcinoma (1.46%), and 2 atypias (0.98%). The diagnostic performance results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78], and NPV: 75% [0.72;0.78]. A large image atlas was created as well as a diagnosis algorithm from the readers' experience. CONCLUSION: With 74% PPV and 75% NPV, D-FFOCT is not yet ready to be used in clinical practice to identify breast cancer. This is mainly explained by the lack of experience and knowledge of this new technic by the four lectors. By training with the diagnosis algorithm and the image atlas, radiologists could have better outcomes allowing quick detection of breast cancer and lymph node involvement. Deep learning could also be used, and further investigation will follow.

Vulvar biopsy: Punch biopsy or cervical forceps biopsy?

OBJECTIVES: The primary objective of our study is to investigate the rate of non-contributory biopsies between punch biopsy(PB) and cervical forceps biopsy(CFB) for a vulvar lesion seen in consultation. The secondary objective of our study is to evaluate the rate of underestimation of a more severe lesion for patients who have undergone vulvar excision. MATERIAL AND METHOD: This is a retrospective, descriptive, and comparative study conducted at three centers. The study population consisted of patients who underwent vulvar biopsy between 2017 and 2022 in a gynecological surgery consultation at two French hospitals, as well as a city office. The biopsy techniques used were punch or cervical forceps biopsy. Quantitative variables were analyzed using the Mann-Whitney test, while Pearson's or Fisher's Xi2 tests were used for qualitative variables. The significance level was set at 5%. RESULTS: We conducted a retrospective study of 179 vulvar biopsies, of which 100 were punch biopsies and 79 were cervical forceps biopsies, from a total of 107 patients. There was no significant difference in the rate of non-contributory biopsies between the PB and CB groups (p = 1). When analyzing the secondary endpoint of our study, which included 68 patients who underwent vulvectomy after vulvar biopsy, we found that 66 patients (97%) had a good correlation between the pathology of the vulvar biopsy and that of the vulvectomy specimen. CONCLUSION: Vulvar biopsy techniques using punch or cervical forceps appear to have similar diagnostic performance and are associated with comparable and low rates of underestimation of invasive lesions.

Impact of cervical excisional dimensions on endocervical margins status in adenocarcinoma in situ of the uterine cervix: A multicenter study from the FRANCOGYN group.

OBJECTIVE: Excisional procedures have a central role in the management of adenocarcinoma in situ of the cervix (AIS). We aimed to evaluate the relationship between the excisional specimen dimensions and the endocervical margin status. METHODS: We conducted a multicentric retrospective study in seven French centers. All cases with proven AIS on a colposcopic biopsy and undergoing an excisional procedure afterwards were included in the analysis. We evaluated the impact of excision length, along with the lateral and anteroposterior diameters on the endocervical margin status. An additional subgroup analysis of the impact of maternal age on endocervical margin status was also conducted. RESULTS: Of the 101 cases of AIS diagnosed on initial biopsy, 95 underwent a primary excisional procedure, among which 80% (n = 76/95) had uninvolved endocervical margins and 20% (n = 19/95) had positive endocervical margins. The excisional specimen length was not significantly related to the endocervical margin status. Conversely, both lateral and antero-posterior diameters were significantly correlated with the negative endocervical margins status: OR = 1,19, 95% CI [1.03, 1.40], p = 0.025, for the lateral diameter and OR = 1.34, 95% CI [1.14, 1.64], p = 0.001 for the antero-posterior diameter. The median lateral diameter was 20 mm, IQR (18, 24) in case of endocervical negative margins vs. 18 mm IQR (15, 24) in case of positive endocervical margins (p = 0.039), and the median anteroposterior diameter was 17 mm IQR (15, 20) in case of negative endocervical margins vs 14 mm IQR (11, 15) in case of positive endocervical margins (p = 0.004), respectively.  Additionally, in patients over 45 years old, endocervical margin were more likely to be positive despite similar excisional dimensions (7/17 (41%) of positive endocercival margins before 45 years old vs 12/78 (15%) after, p = 0.039) CONCLUSIONS: Endocervical margin statues were significantly related to the transverse diameters (lateral and anteroposterior diameters), but not to the excision specimen length. Reducing the excised length may lead to fewer post-procedure complications but would still allow to obtain a large proportion of negative endocervical margins.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Endometrial cancer of the very elderly: Management and survival in the Francogyn population.

INTRODUCTION: We aimed to describe management and survival of patients with endometrial cancer (EC) ≥80 years to identify poor prognosis criteria. METHODS: We collected clinical, histologic, surgical and follow-up data for patients with EC ≥ 80 years included in a multicenter French cohort (FRANCOGYN) who underwent primary surgical treatment from 1999 to 2019. The outcomes were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis then a survival time analysis and comparison using the Kaplan Meier method and log-rank test. RESULTS: Of the 1647 patients with EC who received treatment during the study period, 184 (11.17%) were ≥80 years. The mean age was 84 years (±3.34). Thirty-three patients (25.4%) died during the follow-up period and 26 relapsed (18.4%). Forty-nine patients were lost to follow-up (27.37%). The median follow-up time was 15.3 months (4.9-28.8). The median OS and DFS was 16.4 months (6.3-24.9) and 13.6 months (4.5-26.6), respectively. Eighty-three patients received adjuvant therapy (45.11%), out of 95 who had a formal or relative indication. Four patients received adjuvant chemotherapy (2.6%), out of 61 who had a formal or relative indication. Inappropriate or underuse of chemotherapy was significantly associated with a lower median OS of 12.6 months [3.73-24] versus 17.3 months [7.93-41.77] when performed appropriately (HR = 4.14, CI 95% [1.62-10.56]), and a lower median DFS of 10.83 months [3.73-24] versus 17.3 months [7.93-28.5] (HR = 9.04, CI 95% [2.04-40.12]). CONCLUSION: Our results suggest that very elderly patients with EC should receive adjuvant chemotherapy according to the standard care guidelines.

Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming.

BACKGROUND: Adipose tissue is a major component of breast stroma. This study focused on delineating the effects of adipose stem cells (ASCs) derived from breast of healthy women and cancer patients with normal or tumor breast cells. METHODS: The ASCs were induced to differentiate into adipocytes, and the subsequent adipocyte conditioned media (ACM) were evaluated for their fatty acid profile, adipokine secretion and influence on proliferation, migration and invasion on tumoral (MCF-7 and SUM159) and normal (HMEC) human breast cell lines. RESULTS: An enrichment of arachidonic acid was observed in ACM from tumor tissues. Adipose tissues from tumor free secrete twice as much leptin than those from proximal or distal to the tumor. All ACMs display proliferative activity and favor invasiveness of SUM159 cells compared to MCF-7 and HMEC. All ACMs induced lipid droplets accumulation in MCF-7 cells and increased CD36 expression in tumor cells. CONCLUSION: We conclude that among secreted factors analyzed, only arachidonic acid and leptin levels did discriminate ASCs from tumor-bearing and tumor-free breasts emphasizing the importance that other cell types could contribute to the adipose tissue secretome in a tumor context.

[Diagnostic strategy for intrauterine lesions]. / Stratégie diagnostique des lésions intra-utérines.

DIAGNOSTIC STRATEGY FOR INTRAUTERINE LESIONS The diagnostic strategy for intrauterine lesions is a question that arises very frequently in gynecological consultations. Endometrial cancer is more frequent in postmenopausal women and bleeding is the first clinical sign in more than 90% of cases. Pelvic ultrasound and endometrial biopsy have a very important place in the diagnostic strategy. After a single episode of abnormal uterine bleeding and when the ultrasound estimates the thickness of the endometrium to be less than or equal to 4 mm, it is possible to postpone further uterine exploration. In the event of recurrent abnormal uterine bleeding or when the thickness of the endometrium is greater than 4 mm in a postmenopausal woman, additional uterine explorations (hysteroscopy and histology) are recommended. If endometrial cancer is discovered, the key examination is lumbopelvic MRI.

STRATÉGIE DIAGNOSTIQUE DES LÉSIONS INTRA-UTÉRINES La stratégie diagnostique des lésions intra-utérines est une question qui se pose très fréquemment en consultation de gynécologie. Le cancer de l'endomètre survient le plus souvent chez des femmes ménopausées, et les saignements sont le premier signe clinique dans plus de 90 % des cas. L'échographie pelvienne et la biopsie d'endomètre ont une place très importante dans la stratégie diagnostique. Lors d'un épisode unique de saignement utérin anormal et lorsque l'échographie estime l'épaisseur de l'endomètre inférieure ou égale à 4 mm, il est possible de surseoir à une exploration utérine complémentaire. En cas de saignements utérins anormaux récidivants ou lorsque l'épaisseur de l'endomètre est supérieure à 4 mm chez une femme ménopausée, des explorations utérines complémentaires (hystéroscopie et histologie) sont en revanche recommandées. En cas de découverte d'un cancer de l'endomètre, l'examen clé est l'IRM lombopelvienne.

[Evolution of endometrial cancer surgery]. / Évolution de la chirurgie des cancers de l'endomètre.

Minimally invasive surgery (laparoscopic or robotic assisted) is currently recommended when surgery is envisaged, including for patients in the high risk group. The place of the uterine manipulator in this indication still needs to be clarified by prospective studies. The indocyanine green sentinel lymph node procedure has become the reference technique for lymph node staging of FIGO stages I and II regardless of histological type. Management must be carried out in a specialized institution by a team specialised in the gynaecological cancers.

Concernant le cancer de l'endomètre, lorsqu'une chirurgie est envisagée, la voie miniinvasive (coelioscopique ou robot-assistée) est actuellement recommandée, y compris pour les patientes du groupe à haut risque. La place du manipulateur utérin dans cette indication doit encore être précisée par des études prospectives. La procédure du ganglion sentinelle au vert d'indocyanine est par ailleurs devenue la technique de référence pour la stadification ganglionnaire des stades FIGO I et II quel que soit le type histologique. La prise en charge doit être assurée dans un établissement spécialisé, par une équipe spécialisée dans les cancers gynécologiques.

Presentation and Prognosis of Primary Expansile and Infiltrative Mucinous Carcinomas of the Ovary.

Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic/para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.

Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied.